March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
The Impact Of Col8a2 Gene Mutations On Mouse Corneal Stromal Architecture
Author Affiliations & Notes
  • Frances E. Jones
    Optometry & Vision Sciences, Cardiff University, Cardiff, United Kingdom
  • Huan Meng
    Wilmer Eye Institute at Johns Hopkins, Baltimore, Maryland
  • Robert D. Young
    Optometry & Vision Sciences, Cardiff University, Cardiff, United Kingdom
  • Albert S. Jun
    Wilmer Eye Institute at Johns Hopkins, Baltimore, Maryland
  • Andrew J. Quantock
    Optometry & Vision Sciences, Cardiff University, Cardiff, United Kingdom
  • Footnotes
    Commercial Relationships  Frances E. Jones, None; Huan Meng, None; Robert D. Young, None; Albert S. Jun, None; Andrew J. Quantock, None
  • Footnotes
    Support  EPSRC Grant EP/F034970/1 (AJQ), NIH Grant EY019874 (ASJ). FEJ is a postgraduate student sponsored by EPSRC
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 1093. doi:
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      Frances E. Jones, Huan Meng, Robert D. Young, Albert S. Jun, Andrew J. Quantock; The Impact Of Col8a2 Gene Mutations On Mouse Corneal Stromal Architecture. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1093.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Fuchs endothelial corneal dystrophy (FECD) is one of the leading causes of corneal vision loss. Missense mutations (L450W and Q455K) in the COL8A2 gene, which encodes the alpha-2 collagen VIII subunit of the procollagen molecule, are associated with early onset FECD in humans. The purpose of this study was to investigate how homologous mutations in the mouse Col8a2 gene might affect the architecture of the corneal extracellular matrix.

Methods: : The corneas of 5-month-old mice with Col8a2L450W/L450W or Col8a2Q455K/Q455K homozygous knock-in gene mutations were stained with Cuprolinic blue and examined by transmission electron microscopy, along with those of age-matched wild type mice. Corneas were categorized into enzyme digested groups: i) keratanase, ii) chondroitinase ABC, and iii) non-enzyme treated. Post-operative human FECD tissue, kindly provided by Peter Watson, FRCOpth, Cambridge, UK, was similarly examined.

Results: : Electron micrographs of Col8a2 mutant mice revealed that the structural relationships between the water-binding proteoglycans (PGs) in the corneal stroma - keratan sulfate and chondroitin/dermatan sulfate - and the type I/V hybrid collagen fibrils were unchanged by the mutation. This was found to be the case in the FECD stroma in humans, too. Collagen architecture was essentially unchanged in the mutant mice and human FECD stroma, although there were signs of mild localised edema in the posterior stroma of FECD patient corneas and murine Col8a2 Q455K/Q455K corneas as evidenced by focal areas of increased collagen fibril spacing.

Conclusions: : The distribution and association with collagen, of stromal PGs in 5-month-old Col8a2 mice corneas is similar to that in normal murine stroma, suggesting that PGs are not likely to be involved in early onset manifestations of FECD in this animal model. In some sections collagen interfibrillar spacing appeared to increase focally in the posterior stroma of human corneas, which may well be a characteristic of edema commonly observed in patients with late onset FECD. No widespread corneal edema was evident in Col8a2 mutant mice, although the occasional sign of focal edema in Col8a2 Q455K/Q455K corneas resembled the human condition. This may be linked to the fact that Col8a2L450W/L450W mutant mice show only a 10% reduction in endothelial cell count at 5 months of age, whereas mutant Col8a2Q455K/Q455K corneas at the same age display a 27% decrease in endothelial cell numbers.

Keywords: cornea: stroma and keratocytes • cornea: basic science 

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